While human immunodeficiency virus (HIV) infection, which results in AIDS, is a relatively new infection in the human population, it has quickly risen to the foremost health problem in the world. HIV/AIDS is now the leading cause of death in sub-Saharan Africa, and is the fourth biggest killer worldwide. While better treatment methods are now known to prolong the life of patients with HIV infection, there is still no cure.
The HIV infection of CD4+ cells leads to progressive loss of CD4+ cells, causing the incidence of opportunistic infections and even death. Although there are divergent views on the pathogenesis of AIDS, one of generally accepted views is that oxidative stress with excessive oxygen free radicals caused by viral infection can activate the immune system (immune activation), and lead to progressive CD4+ cell depletion (Wanchu et al., 2009, AIDS Research and Human Retroviruses 25(12):1307-1311; Polyakov et al., Int Conf AIDS, 1992 Jul. 19-24; 8: 32 (abstract no. PuA 6129)). Oxygen free radicals also reported to have relationship with HIV replication (Oxidative stress and HIV infection: target pathways for novel therapies? Future HIV Therapy, 2(4):327-338, 2008). Because superoxide dismutase (SOD) is the most important antioxidant enzyme which catalyzes the dismutation of superoxide anion free radical to generate less toxic hydrogen peroxide and oxygen, it has been used to treat various oxygen free radical-related diseases (Winterbourn, 1993, Free Radical Biology & Medicine, 14:85-90). Studies indicated that SOD gene expression was inhibited in HeLa cells which were infected with HIV tat gene, and reduced antioxidant enzyme defense leads to rapid depletion of plasma thiol (Flores et al., Proc. Natl. Acad. Sci. USA, 1993; 90; 7632-7636). It was found that lecithinized SOD (PC-SOD) inhibits human HIV types 1 and 2 in MT-4 cells (Premanathan, et al., AIDS research and human retroviruses, 13(4), 1997).
Modern anti-HIV drugs target several different stages of the HIV life cycle, and several of the enzymes that HIV requires to replicate and survive. Some of the commonly used anti-HIV drugs include nucleoside reverse transcriptase inhibitors such as ddI, AZT, d4T, 3TC and tenofovir; non-nucleoside reverse transcriptase inhibitors such as nevirapine, efavirenz and delavirdine; protease inhibitors such as saquinavir, amprenavir, lopinavir, ritonavir and indinavir. However, in many HIV infected patients, none of these antiviral drugs, alone or in combination, is effective to prevent the progression of chronic infection or treat acute AIDS. The high mutation rate of the HIV virus and associated emergence of HIV strains resistant to drugs is one large factor that results in the inability to effectively treat HIV infection. Further, the modern anti-HIV drugs are expensive. In addition, the majority of currently available antiviral drugs of HIV show mitochondrial toxicity (Lewis, 1995, Mitochondrial toxicity of antiviral drugs, Nature Med 1:417-422). For example, the mitochondrial toxicity of AZT (zidovudine) results from mutation in mitochondrial DNA caused oxygen free radicals (Hayakawa et al., Biochem Biophys Res Commun, 1991, 176:87-93).
Although oxygen free radicals were reported to be associated with HIV replication and the destruction of CD4+ T cells, several clinical trails with antioxidants indicated further trials were needed to determine whether they had a beneficial effect in the treatment of HIV-infected individuals (Effect of N-acetylcysteine (NAC) treatment on HIV-1 infection: a double-blind placebo-controlled trial, European Journal of Clinical Pharmacology, 50(6):457-461, 1996; Improvement of immune functions in HIV infection by sulfur supplementation: Two randomized trials, Journal of Molecular Medicine, 78(1):55-62, 2000; Restoration of Blood Total Glutathione Status and Lymphocyte Function Following α-Lipoic Acid Supplementation in Patients with HIV Infection, The Journal of Alternative and Complementary Medicine, 14(2): 139-146, 2008).
Accordingly, an inexpensive yet effective therapeutic and prophylactic treatment for HIV infection is desired. The treatment should be easily administered to those who are susceptible to or already have the virus. The present invention addresses these issues, as well as the problems presented in the prior art.